2. Academic Validation
  3. In Vitro Inhibitory Effects of 8-O-Demethylmaritidine and Undulatine on Acetylcholinesterase and Their Predicted Penetration across the Blood-Brain Barrier

In Vitro Inhibitory Effects of 8-O-Demethylmaritidine and Undulatine on Acetylcholinesterase and Their Predicted Penetration across the Blood-Brain Barrier

  • J Nat Prod. 2015 Jun 26;78(6):1189-92. doi: 10.1021/acs.jnatprod.5b00191.
Lucie Cahlíková 1,  Daniel I Pérez 2,  Šárka Štěpánková 3,  Jakub Chlebek 1,  Marcela Šafratová 1,  Anna Hošt'álková 1,  Lubomír Opletal 1
Affiliations

Affiliations

  • 1 †ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
  • 2 ‡Centro de Investigaciones Biológicas, Avenida Ramiro de Maeztu, 9, 28040 Madrid, Spain.
  • 3 §Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentská 95, 532 10 Pardubice, Czech Republic.
PMID: 26030662 DOI: 10.1021/acs.jnatprod.5b00191
Abstract

Alzheimer's disease is the most common cause of dementia. Currently, acetylcholinesterase (AChE) inhibition is the most widely used therapeutic treatment. A large number of naturally occurring compounds have been found to inhibit AChE. In this report the mechanism of AChE inhibition of two Amaryllidaceae alkaloids, 8-O-demethylmaritidine (1) and undulatine (2), and their possible penetration across the blood-brain barrier have been studied. Both compounds act via a mixed inhibition mechanism. Based on the parallel artificial permeation assay (PAMPA) for the prediction of blood-brain barrier (BBB) penetration, only 2 should be able to cross the BBB by passive permeation.

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